Dopamine plays a critical role in drug reinforcement and addiction. PET studies reveal that drugs induce large, rapid increases in extracellular dopamine in the brain, mimicking physiological dopamine firing but being more intense and prolonged. These increases are linked to salient stimuli, enhancing attention, arousal, and motivation. Repeated drug use may raise the threshold for dopamine activation, leading to reduced dopamine D2 receptor availability and impaired brain function in regions like the orbitofrontal cortex, cingulate gyrus, and dorsolateral prefrontal cortex. These regions are involved in salience attribution, inhibitory control, and executive function, which are disrupted in addiction. Drug cues enhance dopamine signaling, driving the motivation to seek drugs. Reduced dopamine function in addicts also decreases sensitivity to natural reinforcers. Therapeutic interventions targeting dopamine function and cortical projection regions could improve prefrontal function, inhibit impulsivity, and reduce compulsive drug use. Imaging studies show that dopamine receptor availability is lower in addicts, contributing to addiction vulnerability. Factors such as D2 receptor levels, dopamine release, and striatal activity influence the risk of addiction. Sex differences and individual variability in dopamine systems may also affect susceptibility. Understanding these mechanisms informs treatment strategies aimed at restoring dopamine function and reducing drug-seeking behavior.Dopamine plays a critical role in drug reinforcement and addiction. PET studies reveal that drugs induce large, rapid increases in extracellular dopamine in the brain, mimicking physiological dopamine firing but being more intense and prolonged. These increases are linked to salient stimuli, enhancing attention, arousal, and motivation. Repeated drug use may raise the threshold for dopamine activation, leading to reduced dopamine D2 receptor availability and impaired brain function in regions like the orbitofrontal cortex, cingulate gyrus, and dorsolateral prefrontal cortex. These regions are involved in salience attribution, inhibitory control, and executive function, which are disrupted in addiction. Drug cues enhance dopamine signaling, driving the motivation to seek drugs. Reduced dopamine function in addicts also decreases sensitivity to natural reinforcers. Therapeutic interventions targeting dopamine function and cortical projection regions could improve prefrontal function, inhibit impulsivity, and reduce compulsive drug use. Imaging studies show that dopamine receptor availability is lower in addicts, contributing to addiction vulnerability. Factors such as D2 receptor levels, dopamine release, and striatal activity influence the risk of addiction. Sex differences and individual variability in dopamine systems may also affect susceptibility. Understanding these mechanisms informs treatment strategies aimed at restoring dopamine function and reducing drug-seeking behavior.